Process of the preparation of hydroxyfurenones

ABSTRACT

A novel technique for the preparation of 4-hydroxy-5-alkyl-3-oxo-2H-furans is disclosed wherein the reaction product of an alpha-alkyl diglycolic acid diester and an oxalic acid diester is cyclized, hydrolyzed and decarboxylated. Alternatively, the corresponding 2,5-dialkyl product can be prepared by an intermediate alkylation step.

This is a division of application Ser. No. 879,307, filed Feb. 21, 1978,now U.S. Pat. No. 4,127,592.

The present invention relates to a novel process for preparing4-hydroxy-5-alkyl-3-oxo-2H-furans and4-hydroxy-2,5-dialkyl-3-oxo-2H-furans having the general formula:##STR1## or tautomeric forms thereof where R₁ represents an alkylradical having 1 to 6 carbon atoms and R₂ represents hydrogen or analkyl radical having 1 to 4 carbon atoms. The invention furthermorerelates to novel intermediates used in the said process.

In recent years furan derivatives of the above type have receivedconsiderable attention from researchers interested in the flavoring art.A survey of the literature reveals that these compounds are useful in avery wide range of foodstuff and beverage applications. For example,U.S. Pat. No. 3,647,825 states that 4-hydroxy-5-methyl-3-oxo-2H-furanhas been added with beneficial results to bread, biscuits, candy,chocolate, meat and processed meat, milk products, processed foodprepared from eggs, fresh and smoked fish and vegetable, also topowdered soup concentrates, dried fruits and nuts, canned fruits, softdrinks, liqueur, wine, whiskey, instant coffee, but also cigars andcigarettes, chewing gum and oral hygiene preparations such astoothpastes, mouth washes and mouth wash concentrates.

U.S. Pat. No. 3,887,589 teaches the use of2,5-diethyl-4-hydroxy-3-oxo-2H-furan in bakery products to provide amore pleasant taste and a fresher impression. U.S. Pat. No. 3,576,014teaches using 4-hydroxy-2-methyl-5-ethyl-3-oxo-2H-furan and4-hydroxy-2-ethyl-5-methyl-3-oxo-2H-furan as a raspberry or gooseberryflavoring. U.S. Pat. No. 3,709,697 teaches4-hydroxy-2-methyl-5-ethyl-3-oxo-2H-furan and4-hydroxy-2,5-diethyl-3-oxo-2H-furan as additives to impart or enhance ameat flavor.

Many syntheses have been suggested for the preparation of furans of theabove-identified type. However, all of these are either non-economicalmultistep laboratory methods which cannot profitably be applied to theproduction of the compounds on a commercial scale or they utilize veryexpensive natural products such as rhamnose (cf. Proc.Am.Soc. BrewingChemists 84, (1963)) which can be obtained only in small insufficientquantities of unpredictable quality and which therefore are not suitablestarting materials for production of the furans on a commercial scale.For techniques which have heretofore been proposed for preparing thesecompounds, reference can be had to J.Org.Chem. 31, 2391-4 (1966), J.Org. Chem. 38, 123-125 (1973), and to U.S. Pat. Nos. 3,709,697;3,647,825; 3,887,589; 3,576,014; 3,694,466; 3,651,097; 3,853,918;3,629,292; and 3,629,293; British Pat. No. 1,440,270; Swiss Pat. No.565,168.

In accordance with this invention, it has now been found that furanderivatives of the class above designated can be prepared in atechnically very simple and commercially feasible manner.

The novel process of this invention comprises the steps

(a) condensing a dialkyl-α-alkyl diglycolic acid ester with an oxalicacid diester in the presence of an alkaline condensing agent to preparethe disodium salt of 2-carbalkoxy-3,4-dihydroxy-5-alkyl furan;

(b) hydrolyzing the carbalkoxy group of said disodium salt;

(c) decarboxylating the hydrolyzed product; and

(d) recovering 4-hydroxy-5-alkyl-3-oxo-2H-furan.

Optionally, the disodium salt of 2-carbalkoxy-3,4-dihydroxy-5-alkylfuran can be alkylated to a 2,5-dialkyl homologue by alkylating it witha lower alkyl halide prior to the hydrolysis step.

The process of the invention is represented schematically by thereaction schemes diagrammed in the drawing where R₁ has the meaningspecified above, R₃ is an alkyl radical having 1 to 4 carbon atoms, R₄is an alkyl radical fitting the description of the alkyl radicalrepresented by R₂ above, M is an alkali metal ion and X is a halogen.

Starting materials I and II are easily prepared compounds. Compound I asa dialkyl α-alkyl diglycolic acid ester. It can be prepared by reactionof an alkyl halo-acetate (bromo- or chloro-) and an alkyl ester of anα-hydroxy carboxylic acid. This synthesis is described by A.Soladie-Cavallo and P. Vieles in Bull.Soc.Chim.France, 1967, page 517 etseq. The diethyl and dimethyl esters are preferred. Dialkyl oxolates(II) are cheap, commercially available compounds. The diethyl anddimethyl esters are very common and are accordingly preferred for use inthe reaction. Other lower alkyl esters can, however, be used withequally good results.

The reaction between the alpha-alkyl diglycolic acid diester and thedialkyl oxalate produces the disodium salt of2-carbalkoxy-3,4-dihydroxy-5-alkyl furan, III. The reaction is carriedout in an inert diluent or solvent in the presence of an alkalinecondensing agent, preferably an alkali metal alkoxide of a 1 to 4 carbonalcohol or an alkali metal hydride. Condensing agents based on any ofthe alkali metals e.g. lithium, potassium and sodium, can be used. Thepreferred alkaline condensing agents are sodium methoxide, sodiumethoxide, and sodium hydride. Some of the intermediate compounds of thereaction are sometimes referred to hereinafter as sodium salts. Itshould be understood that these compounds could equally well be otheralkali metal salts.

By an inert diluent or solvent is meant an organic liquid which does notitself enter into the reaction or which cannot react in another way withthe other reactants. The diluent can be either polar or non polar. Thusthere can be used such organic liquids as aliphatic and aromatichydrocarbons, alcohols, dimethyl formamide, dimethyl sulfoxide, ethers,and nitriles. The choice of diluent can affect the temperature at whichthe reaction is carried out but necessary conditions for a particulardiluent are easily determined experimentally.

In carrying out reaction scheme A equimolar quantities of thedialkyl-α-alkyl diglycolic acid ester and the dialkyl oxalate, I and II,are added to a solution or suspension of two equivalents of the alkalinecondensing agent in the inert diluent at low temperature. Reactionbegins substantially immediately upon contact of reagents I and II. Itis preferable to remove the alcohol formed by the condensation reactionas the reaction proceeds as this helps to force the reaction tocompletion, resulting in better yields. This is not critical to theformation of the intermediate disodium salt of2-carbalkoxy-3,4-dihydroxy-5-alkylfuran. When the reaction is complete,the disodium salt can be recovered as such, acidified to its3,4-dihydroxy form and recovered or subjected immediately to thehydrolysis and decarboxylation steps to convert it to4-hydroxy-5-alkyl-3-oxo-2H-furan or it can be used in reaction scheme Bwithout any intermediate recovery operations.

In carrying out reaction scheme B in which the intermediate compound IIIis alkylated to form a 2,5-dialkyl substituted product the solvents ordiluents used in scheme A can be used, but it is preferable to employ adipolar, aprotic diluent or solvent. The reaction proceeds more rapidlyin the presence of such a solvent. Dimethyl sulfoxide,dimethylformamide, or a mixture of at least about 10% or more by weightof one of these in toluene or another polar or apolar organic liquid ispreferred.

Prior to carrying out the alkylation, it is helpful to convert thedisodium salt to the monosodium salt by adding the calculated amount ofan anhydrous organic acid or a mineral acid to the reaction mixture. Themonosodium salt has been found to be more soluble in the organicreaction medium and the alkylation reaction proceeds more rapidly andmore selectively when carried out on this salt than with the disodiumsalt.

The alkylation reaction is carried out using an equimolar amount, basedon compound III of an alkyl halide of 1 to 4 carbon atoms. Any alkylhalide fitting this description can be used, e.g. the alkyl chlorides,alkyl bromides, and alkyl iodides. The reaction can be conducted atabout 20° to 80° C. and takes place in about 1 to 20 hours dependingupon the temperature. Completion of the alkylation reaction is indicatedby a steady pH reading of about 6.5 to 7.5.

As mentioned above in the case of compound III, the initial alkylationproduct VII, can be recovered as such, or subjected immediately to thehydrolysis and decarboxylation steps without any intermediate recoverysteps.

Conversion of the intermediate compounds to their intended finalproducts is effected in the same way for both reaction schemes A and B.In each case, the ester is hydrolyzed to its alkali salt form andthereafter decarboxylated.

Hydrolysis of the ester can be carried out by the use of an alkali metalhydroxide in a manner known to the art for effecting hydrolysis of anester. The resulting de-esterified carboxylic acid group is not stableand decarboxylation takes place spontaneously upon neutralization oracidification thereof.

As suggested hereinabove, the intermediate reaction products IV and VIIcan be isolated and recovered if desired. These can be further processedas described hereinabove at a later time by hydrolyzing anddecarboxylating as described. In particular, it is useful to recoverproduct IV in the intermediate state as it can thereafter be used toprepare either the alkylated final product as needed.

These intermediate products, 2-carbalkoxy-3,4-dihydroxy-5-alkyl furan(IV) which may exist to a small extent in its keto-enol tautomericforms, and 2-carbalkoxy-4-hydroxy-2,5-dialkyl-3-oxo-2H-furan (VII) arenovel compounds. In addition to their utility as intermediates in theinstant process, they have been found to be useful additives to severaltypes of flavors because of their ability to enhance the sweetnesscausing a richer, more balanced taste by improving the body notes. Inthis respect they are useful in a variety of applications such as e.g.pastries, soft drinks, confectionaries, and as components of artificialsweetener compositions. The following examples illustrate the invention.

EXAMPLE 1 2-Carbethoxy-5-methyl-3,4-dihydroxy-furan

In a 6-L three-necked flask fitted with a mechanical stirrer, a droppingfunnel, a thermometer, a 30 cm Vigreux column connected to a deflegmatorand a gas inlet tube, is placed a suspension of 408 g of sodium ethoxidein 3 L of dry toluene. To the stirred suspension is added, undernitrogen, at 0° C., 438 g of diethyl oxalate over a period of 75minutes. To the yellow reaction mixture is then added, at 0°-2° C., 612g of diethyl α-methyldiglycolate (A. Solladie-Cavallo and P. Vieles,Bull. Soc. Chim. France 1967, 517), over a period of 90 minutes. Thereaction mixture is stirred at room temperature for an additional 2hours. The reaction mixture is then warmed up gradually and anethanol-toluene mixture is distilled off till the vapour temperaturereaches 107° C. The reaction mixture is cooled to room temperature andstirred for 30 minutes with 2 L of water. The reaction mixture istransferred to a separatory funnel, the toluene layer is separated offand the water layer is washed successively with diisopropyl ether andpentane. The aqueous solution is acidified with concentratedhydrochloric acid. The temperature is maintained at 0° C. throughout theacidification. The solid product is filtered off and dried, yielding 425g 76% of 2-carbethoxy-5-methyl-3,4-dihydroxy furan; recrystallized fromalcohol, m.p. 120°-121° C.

NMR (CDCl₃), δ 1.40 (3H, t), 2.28 (3H, s), 4.40 (2H, q), 6.0 (2H,broad).

EXAMPLE 2 2-Carbethoxy-5-methyl-3,4-dihydroxy furan

In a 2 L three-necked flask fitted with a mechanical stirrer, athermometer, a nitrogen inlet tube and a reflux condensor protected by acalcium chloride tube, is placed a solution of 102 g of diethylα-methyldiglycolate and 73 g of diethyl oxalate in 1 L of drydimethylformamide. To the stirred reaction mixture is added at roomtemperature 24 g of sodium hydride and 0.5 ml of ethanol. The reactionmixture is then heated under nitrogen to 90° C. when an exothermicreaction accompanied by hydrogen evolution is observed. The temperatureis maintained at 110° C. for an additional 15 minutes. The reactionmixture is cooled then to room temperature and the solvent is removedunder vacuum. The residue is dissolved in water and the aqueous solutionis acidified with concentrated hydrochloric acid. The temperature ismaintained at 0° C. throughout the acidification. The solid product isfiltered off and dried.

Yielding 39.5 g (42.5%) of 2-carbethoxy-5-methyl-3,4-dihydroxy furanm.p. 119°-120° C.

EXAMPLE 3 4-Hydroxy-5-methyl-3-oxo-2H-furan

A solution of 37.2 g of 2-carbethoxy-5-methyl-3,4-dihydroxy furan and 32g of sodium hydroxide in 450 ml of water is kept at room temperature,under nitrogen, for 20 hours.

The reaction mixture is acidified (pH3) with concentrated hydrochloricacid, then stirred at 50° C. for 4 hours, and continuously extracted for6 hours with ether. The ether extract is dried and concentrated undervacuum until the total volume of the solution is reduced to about 50 ml.The ether solution is cooled to -70° C. and filtered. The solid productis washed with pentane and dried, yielding 13 g (57%) of4-hydroxy-5-methyl-3-oxo-2H-furan, recrystallized from alcohol-ether,m.p. 128.2°-129.6° C.

NMR (CDCl₃), δ 2.26 (3H, t), 4.52 (2H, q), 6.9 (1H, broad).

EXAMPLE 4 4-Hydroxy-5-methyl-3-oxo-2H-furan

In a 4 L three-necked flask fitted with a mechanical stirrer, a droppingfunnel, a thermometer, a 30 cm Vigreux column connected to a deflegmatorand a gas inlet tube, is placed a suspension of 408 g of sodium ethoxidein 3 L of dry toluene. To the stirred suspension is added, undernitrogen, at 0°-5° C., 438 g of diethyl oxalate over a period of 75minutes. To the yellow reaction mixture is then added, at 4°-6° C., 612g of diethyl α-methyldiglycolate over a period of 90 minutes. Thereaction mixture is stirred at room temperature for an additional twohours. The reaction mixture is then warmed up gradually and the ethanoltoluene mixture is distilled off till the vapour temperature reaches107° C. The reaction is then cooled to room temperature and stirred for30 minutes with 2 L of water. The reaction mixture is transferred to aseparatory funnel, the toluene layer is separated off and the waterlayer is washed with ether. After an addition of 240 g of sodiumhydroxide the aqueous layer is kept at room temperature, under nitrogen,for 20 hours. The reaction mixture is acidified (pH3) with concentratedhydrochloric acid, then stirred at 30° C. for 2 hours and continuouslyextracted for 10 hours with ether. The ether extract is dried and thesolvent is removed under vacuum. The solid residue is recrystallizedfrom ethanol yielding 243 g (71%) of 4-hydroxy-5-methyl-3-oxo-2H-furan,m.p. 130°-130.5° C.

EXAMPLE 5 4-Hydroxy-5-methyl-3-oxo-2H-furan

Example 4 is repeated substituting dimethyl oxalate for diethyl oxalateand dimethyl α-methyldiglycolate for diethyl α-methyldiglycolate. Thereis obtained 253 g (74%) of 4-hydroxy-5-methyl-3-oxo-2H-furan, m.p.129.5°-130° C.

EXAMPLE 6 4-Hydroxy-5-methyl-3-oxo-2H-furan

In a 2 L three-necked flask fitted with a mechanical stirrer, a droppingfunnel, a thermometer and reflux condenser is placed a solution of 108 gof sodium methoxide in 500 ml of methanol. To the stirred solution isadded at 0°-10° C., 146 g of diethyl oxalate over a period of 30minutes. To the reaction mixture is then added at 0°-10° C. 204 g ofdiethyl α-methyldiglycolate over a period of 120 minutes. The reactionmixture is then stirred at reflux temperature for an additional 13hours. The solvent is distilled off and the residue is dried at 100° C.under vacuum. The dried residue is dissolved in 600 ml of 15% sodiumhydroxide solution. The basic solution is kept at room temperature for20 hours. The reaction mixture is then acidified and continuouslyextracted with ether. The ether extract is dried and the solvent isremoved under vacuum. The solid residue is recrystallized from alcoholyielding 69 g (60%) of 4-hydroxy-5-methyl-3-oxo-2H-furan, m.p.130°-130.5° C.

EXAMPLE 7 2-Carbethoxy-2,5-dimethyl-3-oxo-4-hydroxy-2H-furan

In a 0.5 L three-necked flask fitted as described in Example 1, isplaced a suspension of 27.2 g of sodium ethoxide in 180 ml of drytoluene and 20 ml of dry dimethylformamide. To the stirred suspension isadded at 0° C. 29.2 g of diethyl oxalate over a period of 15 minutes. Tothe yellow reaction mixture is then added at 0°-5° C. 40.8 g of diethylα-methyldiglycolate over a period of 15 minutes. The reaction mixture isstirred at room temperature for an additional 30 minutes. The reactionmixture is then warmed up gradually and the ethanol-toluene mixture isdistilled off till the vapour temperature reaches 107° C. The reactionmixture is then cooled to 0° C. and 9.2 g of formic acid is addedfollowed by a solution of 9.2 g ethanol and 0.5 g of sodium iodide in 60ml of dimethyl formamide. Gaseous methyl bromide is bubbled through thevigorously stirred reaction mixture at 40°-50° C. till the pH of thereaction mixture reaches 7.0-7.5. The solvents are removed under vacuum(complete removal of the dimethyl formamide is essential for an optimalisolation of the solid product) and the residue is dissolved in ether.The sodium bromide is filtered off, the ether solution is concentratedunder vacuum and pentane is added to the concentrated ether solution.The ether-pentane solution is cooled and filtered. The solid product iswashed with pentane and dried, yielding 24 g (70%) of2-carbethoxy-2,5-dimethyl-3-oxo-4-hydroxy-2H-furan, recrystallized fromcyclohexane. M.p. 89.2°-89.5° C.

NMR (CDCl₃), δ 1.27 (3H, t), 1.65 (3H, s), 2.32 (3H, s), 4.22 (2H, q),6.00 (1H, broad).

EXAMPLE 8 2-Carbethoxy-2,5-dimethyl-3-oxo-4-hydroxy-2H-furan

Example 7 is repeated substituting methyl iodide for methyl bromide.There is obtained 22 g (64%) of2-carbethoxy-2,5-dimethyl-3-oxo-4-hydroxy-2H-furan.

M.p. 89.8°-90.2° C.

EXAMPLE 9 2-Carbethoxy-2,5-dimethyl-3-oxo-4-hydroxy-2H-furan

Example 7 is repeated substituting methyl chloride for methyl bromide.There is obtained 23 g (67%) of2-carbethoxy-2,5-dimethyl-3-oxo-4-hydroxy-2H-furan.

M.p. 89.7°-90° C.

EXAMPLE 10 2-Carbethoxy-2,5-dimethyl-3-oxo-4-hydroxy-2H-furan

In a 250 ml three-necked flask fitted with a mechanical stirrer and agas inlet tube is placed a solution of 3.4 g of sodium ethoxide in 100ml of ethanol. To the stirred solution is added at room temperature,under nitrogen, 9.3 g of 2-carbethoxy-5-methyl-3,4-dihydroxy-furan and0.5 g of sodium iodide. Gaseous methyl bromide is bubbled through thevigorously stirred reaction mixture at 50°-60° C. till the pH of thereaction mixture reaches 6.5-7.0. The solvent is removed under vacuumand the residue is dissolved in ether. The sodium bromide is filteredoff, the ether solution is concentrated under vacuum and the residue isdistilled through a short Vigreux column;2-carbethoxy-2,5-dimethyl-3-oxo-4-hydroxy-2H-furan is collected at102°-105° C./0.2 mm. Yield 8.1 g (81%), recrystallized from cyclohexane,m.p. 89.8°-90.1° C.

EXAMPLE 11 4-Hydroxy-2,5-dimethyl-3-oxo-2H-furan

A solution of 9 g of 2-carbethoxy-2,5-dimethyl-3-oxo-4-hydroxy-2H-furanand 5.4 g of sodium hydroxide in 50 ml of water is kept at roomtemperature under nitrogen for 20 hours. The reaction mixture isacidified with hydrochloric acid, then stirred at 30° C. for an hour andcontinuously extracted for 6 hours with ether. The ether extract isdried and the solvent is removed under vacuum, the residue is dissolvedin a mixture of 5 ml of dry ether and 5 ml of dry pentane. The solutionis cooled to -10° C. and filtered. The solid product is dried, yielding4.1 g (70%) of 4-hydroxy-2,5-dimethyl-3-oxo-2H-furan. The isolatedproduct is identical (NMR and IR) with a sample of4-hydroxy-2,5-dimethyl-3-oxo-2H-furan prepared from rhamnose (loc cit).M.p. 82°-84° C.

EXAMPLE 12 4-Hydroxy-2,5-dimethyl-3-oxo-2H-furan

In a 20 L three-necked flask fitted with a mechanical stirrer, adropping funnel, a thermometer, a nitrogen inlet tube and a 30 cmVigreux column connected to a deflegmator, is placed a suspension of1512 g of sodium methoxide in 10.5 L of dimethyl formamide. To thestirred suspension is added, under nitrogen, at 5° C., 2044 g of diethyloxalate over a period of 90 minutes. To the yellow reaction mixture isthen added, at 2°-5° C., 2856 g of diethyl 2-methyl-diglycolate over aperiod of 3 hours. The reaction mixture is stirred at room temperaturefor an additional 3 hours. The reaction mixture is then warmed upgradually to 90°-100° C. and kept at that temperature till the alcoholdistillation ceases. The reaction mixture is cooled to room temperatureand 649 g of formic acid is added. Methyl bromide is then bubbledthrough the reaction mixture at 40°-50° C. till the pH of the reactionmixture reaches 7.0-7.5. The solvents are removed under vacuum and theresidue is dissolved in a solution of 2472 g of sodium hydroxide in 9 Lof water. The reaction mixture is kept at room temperature undernitrogen for 20 hours, acidified with hydrochloric acid and thencontinuously extracted with ether. The ether extract is dried and thesolvent is removed under vacuum, the residue is recrystallized fromether yielding 916 g (51%) of 4-hydroxy-2,5-dimethyl-3-oxo-2H-furan,m.p. 80°-82° C.

The isolated product is identical (NMR and IR) with a sample of4-hydroxy-2,5-dimethyl-3-oxo-2H-furan prepared from rhamnose (loc cit).

EXAMPLE 13 4-Hydroxy-2,5-dimethyl-3-oxo-2H-furan

Example 12 is repeated replacing the formic acid by hydrogen chloride.There is obtained 4-hydroxy-2,5-dimethyl-3-oxo-2H-furan in 48% yield,m.p. 80°-82° C.

EXAMPLE 14 4-Hydroxy-2,5-dimethyl-3-oxo-2H-furan

In a 1 L three-necked flask fitted with a mechanical stirrer and a gasinlet tube is placed a suspension of 34 g of sodium ethoxide in amixture of 100 ml of dimethylformamide and 300 ml of toluene. To thestirred suspension is added at room temperature, under nitrogen, 93 g of2-carbethoxy-5-methyl-3,4-dihydroxy-furan. Gaseous methyl bromide isbubbled through the stirred reaction mixture at 30°-40° C. till the pHof the reaction mixture reaches 6.5-7.0. The solvents are removed undervacuum and the residue is dissolved in a solution of 80 g of sodiumhydroxide in 350 ml of water. The reaction mixture is kept at roomtemperature under nitrogen for 20 hours, acidified with hydrochloricacid and continuously extracted with ether. The ether extract is driedand the solvent removed under vacuum, the residue is recrystallized fromether, yielding 41.5 g (65%) of 4-hydroxy-2,5-dimethyl-3-oxo-2H-furan,m.p. 81.5°-83.1° C.

EXAMPLE 15 4-Hydroxy-2-methyl-5-ethyl-3-oxo-2H-furan and4-hydroxy-2-ethyl-5-methyl-3-oxo-2H-furan

In a 1 L three-necked flask fitted with a mechanical stirrer, a droppingfunnel, a thermometer, a nitrogen inlet tube and a reflux condenserprotected by a calcium chloride tube is placed a suspension of 20.4 g ofsodium ethoxide in 180 ml of toluene and 120 ml of dimethylformamide. Tothe stirred reaction mixture is added 55.8 g of2-carbethoxy-5-methyl-3,4-dihydroxy furan. The temperature is maintainedbelow 20° C. throughout the addition. To the clear red solution is added120 g of ethyl bromide over a period of 15 minutes. The reaction mixtureis then stirred at 40° C. for an additional 20 hours. The solvents areremoved under vacuum and the residue is dissolved in ether. The sodiumbromide is filtered off and the ether solution is extracted with cold 5%sodium hydroxide solution. The aqueous solution is acidified withhydrochloric acid. The temperature is maintained at 0° C. throughout theacidification. The acidified aqueous solution is then continuouslyextracted for 6 hours with ether. The ether extract is dried, thesolvent is removed under vacuum and the residue is distilled through ashort Vigreux column. The product is collected as an isomeric mixture of4-hydroxy-2-methyl-5-ethyl-3-oxo-2H-furan (40%) and4-hydroxy-2-ethyl-5-methyl-3-oxo-2H-furan (60%) at 74°-76° C./0.3 mm.Yield 15 g (35%), n_(D) ²⁰ 1.5096.

NMR (CCl₄) δ 0.99 (t), 1.37 (t), 1.85 (m), 2.25 (s), 2.65 (q), 4.38 (m),7.2 (broad s).

EXAMPLE 16 4-Hydroxy-2-methyl-5-hexyl-3-oxo-2H-furan and4-hydroxy-2-hexyl-5-methyl-3-oxo-2H-furan

In a 1 L three-necked flask fitted with a mechanical stirrer, a droppingfunnel, a thermometer, a nitrogen inlet tube and a reflux condensorprotected by a calcium chloride tube, is placed a suspension of 19.8 gof sodium ethoxide in 130 ml of dry toluene and 15 ml of drydimethylformamide. After stirring for 10 minutes 21.3 g of diethyloxalate is added dropwise, under nitrogen, at 10° C. To the yellowreaction mixture is then added dropwise, at 10°-15° C., 40 g of diethylα-hexyldiglycolate (prepared according to A. Solladie-Cavallo and P.Vieles, Bull. Soc. Chim. France, 1967, 517; bp. 112° C./0.3 mm, n_(D) ²⁰1.4345). The reaction mixture is stirred at room temperature for anadditional 15 minutes and then warmed up gradually. The ethanol-toluenemixture is distilled off till the vapour temperature reaches 110° C. Thereaction mixture is then cooled to 0° C. and 6.9 g of formic acid isadded followed successively by 6.9 g of ethanol and 100 ml of dimethylformamide. Gaseous methyl bromide is bubbled through the vigorouslystirred reaction mixture at 25°-40° C. till the pH of the reactionmixture reaches 7.0-7.5. The solvents are removed completely undervacuum and the residue is dissolved in 200 ml of ether and 24.5 g ofsodium hydroxide in 100 ml of water. The resulting slurry is stirred atroom temperature under nitrogen for 20 hours. The mixture is thenacidified with hydrochloric acid (pH=3.4). The temperature is maintainedat 20° C. throughout the acidification. The acidified aqueous solutionis neutralised with a 10 N sodium hydroxide solution in water till thepH reaches 6.8, then continuously extracted for 6 hours with ether. Theether extract is dried and the solvent is removed under vacuum. Theresidue is distilled through a short Vigreux column. The product iscollected as an isomeric mixture of4-hydroxy-2-methyl-5-hexyl-3-oxo-2H-furan (55%) and4-hydroxy-2-hexyl-5-methyl-3-oxo-2H-furan (45%) at 102° C./0.1 mm. Yieldis 12.5 g (42%), n_(D) ²⁰ =1.4935.

NMR (CDCl₃) δ 0.9, 1.45 (d), 2.28 (d), 2.6 (t), 4.5 (m), 7.3 (broad).

EXAMPLE 17 4-Hydroxy-2-methyl-5-pentyl-3-oxo-2H-furan and4-hydroxy-2-pentyl-5-methyl-3-oxo-2H-furan

Example 16 is repeated substituting diethyl α-pentyldiglycolate(prepared according to A. Solladie-Cavallo and P. Vieles, Bull. Soc.Chim. France, 1967, 517; b.p. 106°-108° C./0.2 mm) for diethylα-hexyldiglycolate in stoichiometrically equivalent amounts. There isobtained in a yield of 52% a mixture of4-hydroxy-2-methyl-5-pentyl-3-oxo-2H-furan (55%) and4-hydroxy-2-pentyl-5-methyl-3-oxo-2H-furan (45%), b.p. 102° C./0.4 mm,n_(D) ²⁰ =1.4956.

NMR (CDCl₃) δ 0.84, 2.20 (d), 2.56 (t), 4.40 (m), 6.9 (broad).

EXAMPLE 18 4-Hydroxy-2-methyl-5-isobutyl-3-oxo-2H-furan and4-hydroxy-2-isobutyl-5-methyl-3-oxo-2H-furan

Example 16 is repeated substituting diethyl α-isobutyldiglycolate(prepared according to A. Solladie-Cavallo and P. Vieles, Bull. Soc.Chim. France, 1967, 517; b.p. 106°-110° C./0.9 mm) for diethylα-hexyldiglycolate in stoichiometrically equivalent amounts. There isobtained in a yield of 57% a mixture of4-hydroxy-2-methyl-5-isobutyl-3-oxo-2H-furan (67%) and4-hydroxy-2-isobutyl-5-methyl-3-oxo-2H-furan (33%), b.p. 97° C./0.9 mm,n_(D) ²⁰ =1.4998.

NMR (CDCl₃) δ 0.98, 1.44 (d), 2.14 (d), 2.51 (d), 4.5 (m), 7.7 (broad).

EXAMPLE 19 4-Hydroxy-2-methyl-5-butyl-3-oxo-2H-furan and4-hydroxy-2-butyl-5-methyl-3-oxo-2H-furan

Example 16 is repeated substituting diethyl α-butyldiglycolate (preparedaccording to A. Solladie-Cavallo and P. Vieles, Bull. Soc. Chim. France,1967, 517; b.p. 90°-91° C./0.2 mm) for diethyl α-hexyldiglycolate instoichiometrically equivalent amounts. There is obtained in a yield of40% an isomeric mixture of 4-hydroxy-2-methyl-5-butyl-3-oxo-2H-furan(50%) and 4-hydroxy-2-butyl-5-methyl-3-oxo-2H-furan (50%), b.p. 104°C./0.7 mm, n_(D) ²⁰ =1.4998.

NMR (CDCl₃) δ 0.95 (3H), 1.44 (d), 2.25 (d), 2.60 (t), 4.43 (m), 6.9(broad).

EXAMPLE 20 4-Hydroxy-2-methyl-5-ethyl-3-oxo-2H-furan and4-hydroxy-2-ethyl-5-methyl-3-oxo-2H-furan

Example 16 is repeated substituting diethyl α-ethyldiglycolate (preparedaccording to A. Solladie-Cavallo and P. Vieles, Bull. Soc. Chim. France,1967, 517; b.p. 80°-81° C./0.2 mm, n_(D) ²⁰ =1.4255) for diethylα-hexyldiglycolate in stoichiometrically equivalent amounts. There isobtained, in a yield of 46%, an isomeric mixture of4-hydroxy-2-methyl-5-ethyl-3-oxo-2H-furan (38%) and4-hydroxy-2-ethyl-5-methyl-3-oxo-2H-furan (62%), n_(D) ²⁰ =1.5111, b.p.80°-82° C./0.6 mm.

EXAMPLE 21 4-Hydroxy-5-ethyl-3-oxo-2H-furan

In a 1 L three-necked flask fitted with a mechanical stirrer, a droppingfunnel, a thermometer, a nitrogen inlet tube and a reflux condensorprotected by a calcium chloride tube, is placed a suspension of 25.2 gof sodium ethoxide in 185 ml of dry toluene. After stirring for 15minutes, 27.1 g of diethyl oxalate is added under nitrogen at 10° C.dropwise. To the yellow reaction mixture is then dropwise added at10°-15° C., 40.5 g of diethyl α-ethyldiglycolate (prepared according toA. Solladie-Cavallo and P. Vieles, Bull. Soc. Chim. France, 1967, 517;b.p. 80°-81° C./0.2 mm, n_(D) ²⁰ =1.4255). The reaction mixture isstirred at room temperature for an additional 12 hours. The reactionmixture is then warmed up gradually and the ethanol-toluene mixture isdistilled off till the vapour temperature reaches 104° C. The reactionis then cooled to room temperature and stirred for 30 minutes with 200ml of water. The reaction mixture is then transferred to a separatoryfunnel, the toluene layer is separated off. To the aqueous layer isadded successively a solution of 15.2 g of sodium hydroxide in 200 ml ofwater and 100 ml of ether. This mixture is stirred at room temperatureunder nitrogen for 20 hours. The reaction mixture is acidified (pH=3)with concentrated hydrochloric acid, then stirred at room temperaturefor 2 hours. The resulting solution is neutralized with 10 N sodiumhydroxide solution in water till the pH reaches 6.8, then continuouslyextracted for 10 hours with ether. The ether extract is dried and thesolvent is removed under vacuum, giving 13.3 g of solid material.Recrystallization from ether afforded 8.3 g (35%) of4-hydroxy-5-ethyl-3-oxo-2H-furan, m.p. 52°-54° C.

NMR (CDCl₃) δ 1.24 (t, 3H), 2.64 (q, 2H), 4.52 (d, 2H), 6.5 (s, 1H).

EXAMPLE 22 4-Hydroxy-5-hexyl-3-oxo-2H-furan

Example 21 is repeated substituting diethyl α-hexyldiglycolate (preparedaccording to A. Solladie-Cavallo and P. Vieles, Bull. Soc. Chim. France,1967, 517, b.p. 112° C./0.3 mm, n_(D) ²⁰ 1.4345) for diethylα-ethyldiglycolate in stoichiometrically equivalent amounts. There isobtained 61 g of solid material. Recrystallization from ether gave 20 g(30%) of 4-hydroxy-5-hexyl-3-oxo-2H-furan, m.p. 51°-52° C.

NMR (CDCl₃) δ 0.9 (3H), 1.3-1.8 (m, 8H), 2.60 (t, 2H), 4.49 (d, 2H), 7.1(Broad, 1H).

EXAMPLE 23 4-Hydroxy-2,5-diethyl-3-oxo-2H-furan

In a 1 L three-necked flask fitted with a mechanical stirrer, a droppingfunnel, a thermometer, a nitrogen inlet tube and a reflux condensorprotected by a calcium chloride tube, is placed a suspension of 68 g ofsodium ethoxide in 375 ml of DMF. To the stirred reaction mixture isadded dropwise, under nitrogen, at 5° C. 73 g of diethyl oxalate. Afterstirring over a period of 15 minutes is then added dropwise at 5°-10° C.109 g of diethyl α-ethyldiglycolate. The reaction mixture is stirred atroom temperature for 12 hours and then the temperature is raisedgradually. The ethanol is distilled off while the reaction mixture iskept at 100° C. for 6 hours. After vigorous stirring the reactionmixture turns into a thick slurry. In total, 37 g of ethanol arecollected. Then the reaction mixture is cooled to 20° C. and 46 g offormic acid is added followed by 89.5 g of ethylbromide over a period of30 minutes and 9 g of sodium iodide. The reaction mixture is thenstirred at 40° C. for an additional 16 hours. The solvent is removedcompletely under vacuum and the residue is dissolved in a solution of88.3 g of sodium hydroxide in 500 ml of water. The resulting slurry isstirred at room temperature under nitrogen for 3 days. The mixture isthen acidified with hydrochloric acid (pH=3). The temperature ismaintained at 20° C. throughout the acidification. The acidified aqueoussolution is neutralized with a 10 N sodium hydroxide solution in wateruntil the pH reaches 6.8, then continuously extracted with ether. After6 hours the ether extract is dried and the solvent is removed undervacuum giving 43.5 g of residue. An additional period of extraction for12 hours gives 18.5 g of material. The combined residues are distilledthrough a short Vigreux column yielding 27 g (35%) of4-hydroxy-2,5-diethyl-3-oxo-2H-furan, b.p. 89° C./0.9 mm, n_(D) ²⁰=1.5090.

NMR (CDCl₃) δ 0.98 (t, 3H), 1.27 (t, 3H), 1.85 (m, 2H), 2.71 (q, 2H),4.40 (m, 1H), 7.4 (broad s, 1H).

EXAMPLE 24

Two cream flavours were prepared by mixing the following ingredients:

    ______________________________________                                                               A     B                                                ______________________________________                                        acetoin                  3,-     3,-                                          diacetyl                 2,-     2,-                                          vanilline                2,-     2,-                                          ethylbutyrate            1,-     1,-                                          maltol                   0,5     0,5                                          δ-decalactone      1,-     1,-                                          ethyllactate             5,-     5,-                                          butyric acid             5,-     5,-                                          caproic acid             0,5     0,5                                          2-carbethoxy-5-methyl-3,4-dihydroxy furan                                                              --      50,-                                         propyleen glycol         980,-   930,-                                                                 1000,-  1000,-                                       ______________________________________                                    

Mixtures A and B were separately added to an 8% sugar solution at alevel of 0.2 g per liter. The testsolutions were tasted and compared.The panel preferred the testsolution containing mixture B over thetestsolution containing mixture A because the testsolution containingmixture B has a richer, sweeter and creamer character than thetestsolution containing mixture A.

EXAMPLE 25

Two strawberry flavours were prepared by mixing the followingingredients:

    ______________________________________                                                             A     B                                                  ______________________________________                                        ethylacetate           2,0     2,0                                            ethylbutyrate          5,0     5,0                                            ethylformate           1,5     1,5                                            ethyl isovalerate      1,0     1,0                                            ethyl caproate         0,5     0,5                                            γ-undecalactone  0,8     0,8                                            ethylphenylglycidate   10,0    10,0                                           ethylbenzoate          2,5     2,5                                            dimethylanthranilate   2,0     2,0                                            methylisopropylphenylpropionaldehyde                                           10% sol..sup.x        0,5     0,5                                            methyloctincarbonate 10% sol..sup.x                                                                  0,5     0,5                                            maltol                 3,5     3,5                                            acetoin                10,0    10,0                                           2-carbethoxy-2,5-dimethyl-3-oxo-4-hy-                                          droxy-2H-furan         --     12,5                                           propylene glycol        960,2  947.7                                                                 1000,0  1000,0                                         ______________________________________                                         .sup.x in propylene glycol                                               

Mixtures A and B were separately added to a drink containing 8% sugarand 0.05% citric acid. The drinks were tasted and compared. The panelpreferred the drink containing mixture B over the drink containingmixture A because the drink containing mixture B had a fuller, sweeterand more balanced strawberry character than the drink containing mixtureA.

What is claimed is:
 1. 2-Carbalkoxy-3,4-dihydroxy-5-alkyl-furan havingthe structural formula ##STR2## where R₁ represents an alkyl radicalhaving 1 to 6 carbon atoms and R₃ represents an alkyl radical having 1to 4 carbon atoms.
 2. 2-Carbalkoxy-4-hydroxy-2,5-dialkyl-3-oxo-2H-furanhaving the structural formula ##STR3## where R₁ represents an alkylradical having 1 to 6 carbon atoms, R₂ represents an alkyl radicalhaving 1 to 4 carbon atoms and R₃ represents an alkyl radical having 1to 4 carbon atoms.
 3. 2-Carbethoxy-3,4-dihydroxy-5-methyl furan. 4.2-Carbethoxy-4-hydroxy-2,5-dimethyl-3-oxo-2H-furan.